Transcript Slide 1

Center for Professional Advancement
Generic Drug Approvals Course
THE DRUG PRICE COMPETITION
AND PATENT TERM RESTORATION
ACT OF 1984: THE BASICS OF THE
WAXMAN-HATCH ACT
Michael A. Swit, Esq.
Vice President
Why The 1984 Law Was Created
 Difficulty in obtaining an ANDA for post-1962
drugs
 Erosion of patent protection for pioneer drugs
due to lengthy FDA approval process
 Increased pressure for competitive pricing
 Federal government’s role as major drug
purchaser
Statute Sections - NDAs
FDCA § 505(b)(1)
“Any person may file with the Secretary [FDA] an application with
respect to any [new] drug . . .” {21 U.S.C. § 355(b)(1)}
FDCA § 505(b)(2)
“An application . . . for a [new] drug for which the [safety and
effectiveness] investigations . . . relied upon by the applicant for approval
of the application were not conducted by or for the applicant and for
which the applicant has not obtained a right of reference or use from the
person by or for whom the investigations were conducted . . .” {21
U.S.C. § 355(b)(2)}
Post-1984 NDA Requirements
 Preclinical and Clinical Data
 For New Chemical Entity, New Indication, or New
Formulation
 Submission of Patent Information
 Eligibility for Patent Extension or Market Exclusivity
 Pediatric Use Assessment
User Fees & Review Schedule – FY2009
 Application with Clinical Data = $1,247,200
 Application without Clinical Data/ Supplement with
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Clinical Data = $623,600
60 Days – FDA Determines if NDA is Accepted for
Filing
180 Days – FDA Presents all Major Deficiencies
10 Months – 1st Target Date for Approval
12 Months – 2nd Target Date for Approval
Post-1984 ANDA Requirements
 Based on a “Reference Listed Drug” (RLD)
 Bioequivalence Data
 Manufacturing Information
 Approval is Limited by Patent Extension and/or
Market Exclusivity
 Limited Eligibility for Market Exclusivity – 180 Days
 No User Fees
Safe Harbor for ANDA R&D on Patent-Protected
RLD
 History: Court held “patent infringement” includes precommercial
testing of product (flurazepam/Dalmane®)
(Roche v. Bolar, Federal Circuit, 1984)
 Waxman Hatch Act -- Overturned the court decision, specifically
declaring that precommercial testing is NOT an infringement (35 USC
Section 271(e)(1))
 Statute Language: Person may make, use or sell a patented drug
during the patent life if solely for uses reasonably related to the
development and submission of information under a federal law which
regulates the manufacture, use or sale of drugs
Safe Harbor for ANDA R&D on PatentProtected RLD
 Safe Harbor -- applies to innovator and generic firms
(Bristol-Myers Squibb v. Rhone-Poulenc Rorer, S.D.N.Y. 2001, aff ’d, 3rd
Circuit, 2003)
 “Reasonably Related” -- means having a decent prospect that the
“use” would generate the kind of information relevant to FDA
approval requirements
 Construed:
 Intermedics v. Ventritex, N.D.Ca. 1991, aff ’d, Federal Circuit, 1993 – clinical
trials on intermediates, yes
 Medtronic v. Lohr, U.S. Supreme Court, 1996 – applies to medical devices
 Integra Life Sciences v. Merck, U.S. Supreme Court, 2005 – preclinical research
to identify future candidate, yes
Basic Requirements for Securing ANDA Approval
 “Listed Drug”
 Conditions of use
 Active ingredient(s)
 Route of administration, dosage form and strength
 Bioequivalent
 Labeling
 CMC
 Certification to patents
 May be delayed by RLD’s market exclusivity
The Concept of the Listed Drug
 Required for ANDA Approval
 Generic must be the same as the RLD
 Before 1984 – Federal Register Notices Declared DESI
Drugs to be “Effective”
 Now Appear in FDA’s Orange Book, updated monthly
Electronic Orange Book
Approved Drug Products
with
Therapeutic Equivalence Evaluations
Current through March 2008
Preface
FAQ
Search by Active Ingredient
Search by Applicant Holder
Search by Proprietary Name
Search by Application No.
The products in this list have been approved under section 505 of the Federal Food, Drug, and Cosmetic
Act.
Drug question email:
[email protected]
U.S. Department of Health and Human Services
Food and Drug Administration
Center for Drug Evaluation and Research
Office of Pharmaceutical Science
Office of Generic Drugs
Updated: May 1, 2008
Electronic Orange Book
 Search in 3 Databases
 Rx
 OTC
 Discontinued
 Request FDA Determination that RLD Was Not Withdrawn from
the Market for Reasons of Safety or Efficacy
 FDA Answers: Approved Discontinued Drug Products Safety and
Effectiveness Determinations
“Same As” RLD
 Conditions of Use, Route of Administration, Dosage
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Form and Strength
Exception: Suitability Petition Requests Approval of
Differences
FDA Must Approve Before ANDA Is Filed
Examples
Advantages/Disadvantages
Effect of Pediatric Study Rule – Denial or Waiver
Bioequivalence
 Clinical Comparison of Generic and RLD
 No Significant Difference in the Rate and Extent to
which the Active Ingredient Becomes Available at the
Site of Drug Action
 Details in Next Lecture
Labeling
 Same as RLD Except for Certain Differences:
 Changes Permitted Under Suitability Petition
 Based on Different Manufacturer
 Based on Patents or Market Exclusivity
 Electronic Version Required As Of June 8, 2004 (21
CFR 314.94(d); 68 FR 69009 (12/11/03))
 Problem Areas
 Copyright
 Trademark/Trade Dress
 Indication “Carve Out”
-- Trade Name
-- USP Specs
-- “Same”?
Chemistry, Manufacturing & Controls
 Include List of Articles Used as Components of the
Drug
 Full Statement of Composition of the Drug
 Full Description of Methods, Facilities, and Controls
Used in Manufacturing, Processing, and Packaging the
Drug
 Samples of the Drug and Components, If Requested
Inactive Ingredients
 Listed on the Product Label and Labeling
 Need Not Be the Same as the RLD
 Exceptions: Parenterals, Ophthalmics, Otics, Topicals
 ANDA may be delayed if formulation contains inactives
never before included in an approved drug of that route of
administration (Qualitative) – Q1
 Or inactives at a higher concentration (Quantitative) – Q2
 If different as to Q1 or Q2, applicant must submit
information to demonstrate the difference has no effect on
the drug’s safety
CDER Inactive Ingredient Search for Approved
Drug Products
Search Results for “peg”
Inactive Ingredient
Route; Dosage Form
Maximum Potency
Apricot Kernel Oil PEG-6
Esters
Topical; Emulsion,
Cream
2.94%
Apricot Kernel Oil PEG-6
Esters
Vaginal; Emulsion,
Cream
2.94%
Corn Oil PEG-6 Esters
Oral; Capsule, Soft
Gelatin
300 mg
Glyceryl Stearate /PEG
Stearate
Oral; Tablet
1.8 mg
Glyceryl Stearate /PEG
Stearate
Oral; Tablet, Coated
1.8 mg
Glyceryl Stearate /PEG
Stearate
Rectal; Suppository
36.85 mg
Organizational Structure of OGD
 Office of the Director
 Division of Bioequivalence
 Divisions of Chemistry (3)
 Division of Labeling and Program Support
 Review Queue – 1st In, 1st Reviewed, But For
 First generic products for which there are no blocking
patents or exclusivities on the RLD
 Clusters of ANDAs for same active ingredient
 Expertise of Reviewers
Statutory Exclusivities Under WaxmanHatch
 New Chemical Entity (NCE) Exclusivity
 Prohibits the filing of an ANDA (or 505(b)(2) NDA) for a
product that contains the NCE for 5 years after approval
of the first NDA.
 (4 years if ANDA includes a Paragraph IV challenge to listed
patent)
 NCE: "a drug that contains no active moiety that has been
approved by FDA in any other [NDA]."
Statutory Exclusivities …
 3-Year Exclusivity
 Available for NDAs which contain:
 Reports of "new" "clinical trials"
 That were "essential to approval" of the NDA
 Conducted or sponsored by the applicant
 FDA may not approve an ANDA or 505(b)(2) NDA for 3
years after approval
 Applies for new indications, Rx  OTC switch, new dosing
regimen, and some other labeling changes.
Statutory Exclusivities -- Other
 Orphan Drug Exclusivity
 7 year exclusivity
 Drugs for rare conditions (<200,000 people in U.S.)
 Pediatric Exclusivity
 6-month extension of existing patent or Waxman-Hatch
exclusivity
 180-day generic (ANDA) exclusivity
“180-Day” or “ANDA” Exclusivity
 Basics:
 First person to file an ANDA with a Paragraph IV certification gets 180
days during which no other ANDA can be approved for that drug
 Must either (a) not be sued by brand co. in 45-day period or (b) prevail in
litigation (or get favorable settlement)
 180 days starts from earlier of:
 Date of first commercial marketing (changed in 2003; used to peg to a
court decision as well)
Present Goals of OGD
 Decrease Time to Approval & Review Backlogs
 Now called GIVE - the Generic Initiative for Value and Efficiency
 Use existing resources to help modernize & streamline
 Hire and train new reviewers
 Enhanced use of electronic programs for handling submissions
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and internal documents
Identify low-risk manufacturing changes that do not require an
intense review
Educate consumers on safety and low-cost of generics
Timely Foreign Inspections (APIs/DMFs)
Implement changes under FDAAA and MMA
FDA Amendments Act of 2007 (FDAAA)
 Post Labeling of RLD 21 days after approval
 Post Approval Package 30 days after approval
 Database For Authorized Generic Drugs
 FDA must publish a complete list on its Internet site of all
authorized generic drugs, updated quarterly
 Drug trade name, brand manufacturer, and date the
authorized generic drug entered the market
 Drugs marketed, sold, or distributed directly or indirectly to
retail class of trade with either labeling, packaging, product
code, labeler code, trade name, or trade mark that differs from
that of the RLD
FDA Amendments Act of 2007 (FDAAA)
 Clinical Trial Registry Databank
 Not required for blood-level bio studies
 May be required for clinical bio studies (e.g., topical dosage
forms) - controversial
 Citizen Petitions
 Shall not delay ANDA approvals unless necessary for public
health
 If delay, 30-day notice to ANDA applicant
 Denial permitted based on Petitioner’s intent to delay
 Certify that Info became known on XX date
OGD Statistics
Year
ANDAs
Received
ANDAs
Approved
Plus Tentative
Approvals
Median
Approval
Times
2001
307
241
310
18.4 Months
2002
361
296
364
18.3 Months
2003
449
284
373
17.3 Months
2004
563
320
413
16.3 Months
2005
766
361
467
16.3 Months
What’s in a Name?
 Drug Price Competition and Patent Term Restoration
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Act of 1984
“Waxman-Hatch Act” – universally called that until 1994
1994 – Republicans take control of Congress – “HatchWaxman Act”
2006 – Democrats take control of Congress
So what do you call it now? – well, the first part of the
statutory name – Drug Price Competition – relates to
Waxman’s role; and the second part – Patent Term
Restoration – refers to Hatch’s role in pushing the 1984
compromise.
 What do you think?
Numerous FDA Guidance Documents
 CDER Guidance Documents on Generic Drugs
 www.fda.gov/cder/guidance/index.htm
 OGD Guidance Documents for ANDAs
 www.fda.gov/cder/regulatory/applications/anda.htm
 CDER Manual of Policies and Procedures (MAPP)
 www.fda.gov/cder/mapp.htm
Questions?
Call, e-mail, fax or write:
Michael A. Swit, Esq.
Vice President
The Weinberg Group Inc.
336 North Coast Hwy. 101
Suite C
Encinitas, CA 92024
Phone 760.633.3343
Fax 760.454.2979
Cell 760.815.4762
[email protected]
www.weinberggroup.com
About your speaker…
Michael A. Swit, Esq., is a Vice President at The Weinberg Group Inc., where he develops and ensures the execution
of a broad array of regulatory and other services to drug and biologics clients seeking to market products in the
United States. His expertise includes FDA development strategies, compliance and enforcement initiatives, recalls
and crisis management, submissions and related traditional FDA regulatory activities, labeling and advertising, and
clinical research efforts.
Mr. Swit has been addressing critical FDA legal and regulatory issues since 1984. His multi-faceted experience
includes serving for three and a half years as corporate vice president, general counsel and secretary of Par
Pharmaceutical, a prominent, publicly-traded, generic drug company and, thus, he brings an industry and commercial
perspective to his work with FDA-regulated companies. Mr. Swit then served for over four years as CEO of
FDANews.com, a premier publisher of FDA regulatory newsletters and other specialty information products for the
FDA-regulated community. His private FDA regulatory law practice has included service as Special Counsel in the
FDA Law Practice Group in the San Diego office of Heller Ehrman White & McAuliffe and with the Food & Drug
Law practice at McKenna & Cuneo, both in the firm’s Washington office and later in San Diego. He first practiced
FDA regulatory law with the D.C. office of Burditt & Radzius.
Mr. Swit has taught and written on a wide variety of subjects relating to FDA law, regulation and related commercial
activities, including, since 1989, co-directing a three-day intensive course on the generic drug approval process and
editing a guide to the generic drug approval process, Getting Your Generic Drug Approved. A former member of the
Food & Drug Law Journal Editorial Board, he also has been a prominent speaker at numerous conferences sponsored
by such organizations as RAPS, FDLI, and DIA. A magna cum laude graduate of Bowdoin College, with high honors
in history, he received his law degree from Emory University Law School and is a member of the California, D.C. and
Virginia bars.